Neoplasm MetastasisPhase 1/2NCT04521621
A Study of Gebasaxturev (V937) in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic Solid Tumors (V937-013)
A Phase 1/2 study testing Gebasaxturev and Pembrolizumab in people with Neoplasm Metastasis, run by Merck Sharp & Dohme LLC at 29 sites in 14 countries.
Trial summary
The purpose of this study is to evaluate the safety, tolerability, and efficacy in participants with advanced/metastatic or recurrent malignancies who receive gebasaxturev (V937) in combination with pembrolizumab (MK-3475). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasm Metastasis
- What is being tested?
- Gebasaxturev and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 29 sitesin 14 countries
- Study dates
- 28 Oct 2020to 25 Jul 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Locally-advanced disease that is not amenable to surgery or radiation, or Stage IV advanced/metastatic solid tumor malignancies
- Histologically- or cytologically-confirmed diagnosis of an advanced/metastatic solid tumor.
- Measurable disease by RECIST 1.1 criteria as assessed by investigator. Target lesions in a previously irradiated area will be considered measurable if progression has been demonstrated in such lesions
- Submitted a baseline tumor sample for analysis. Participants enrolling in Part 2 Cohorts D-F may enroll without submitting a tumor sample if all other enrollment criteria are met.
- Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale obtained within 72 hours prior to the first dose of study intervention
- If participant has known human immunodeficiency virus (HIV)-positive disease, participant must have well-controlled HIV on antiretroviral therapy (ART), per study criteria.
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- Adequate organ function
- Male participants are eligible to participate if they agree to the following during the intervention period and for at least 120 days: Be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR must agree to use contraception unless confirmed to be azoospermic.
- Female participants are eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies:
- Is not a woman of childbearing potential (WOCBP)
- Is a WOCBP and using a contraceptive method that is highly effective, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days after the last dose of study intervention.
- Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- Part 1, All Cohorts: participants must have at least one injectable lesion amenable to injection and/or biopsy.
- Part 1, Cohort A:
- Locally recurrent, inoperable OR metastatic breast cancer treated with at least 1 prior line of therapy in the metastatic setting with skin involvement and/or subcutaneous lesions or accessible lymph nodes amenable to local injection. An exception would be allowed for participants who are not eligible to receive chemotherapy.
- Diagnosis of triple-negative breast cancer (estrogen receptor, progesterone receptor, and HER2-receptor negative status)
- Part 1, Cohort B:
- Histologically confirmed advanced or metastatic head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, hypopharynx, and/or larynx considered incurable and/or treated with no more than 1 previous line of therapy
- Tumors must be PD-L1+
- Documentation of HPV status for oropharyngeal cancers. Other HNSCC subtypes may submit HPV testing, but is not required.
- Part 1, Cohort C:
- Histologically confirmed cutaneous squamous cell carcinoma (cSCC) as the primary site of malignancy
- Recurrent/metastatic disease only: Has metastatic disease defined as disseminated disease distant from the initial/primary site of diagnosis and/or with a history of locally-recurrent disease previously treated with surgery and/or radiotherapy, which is now incurable
- Locally-advanced disease only: Must be ineligible for surgical resection per study criteria, and must have received prior radiation therapy to the index site or deemed ineligible for radiation therapy
- Part 2, Solid Tumors+Liver Metastases Dose Level 1-3 arms:
- Histologically-confirmed advanced/metastatic solid tumor that has progressed on all treatment known to confer clinical benefit
- Metastatic liver lesion(s) not exceeding one-third of the total liver volume AND a minimum of one injectable liver lesion
- Part 2, Cohort D:
- Advanced hepatocellular carcinoma (HCC) following progression on, or intolerance to, sorafenib or lenvatinib with no curative options
- Diagnosis of HCC confirmed by radiology, histology, or cytology
- Child-Pugh Class A score
- If a participant has a history of hepatitis C virus (HCV) infection, then the participant must have been successfully treated for this condition
- Controlled (treated) hepatitis B participants will be allowed if they meet protocol-specified criteria
- Participants who are anti-hepatitis B core (HBc) positive, negative for hepatitis B surface antigen (HBsAg), negative or positive for anti-hepatitis B surface (HBs), and who have an HBV viral load under 100 IU/mL, do not require HBV anti-viral prophylaxis
- Part 2, Cohort E:
- Histologically- or cytologically-confirmed diagnosis of locally advanced, unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma
- Received at least one prior line of therapy that includes a platinum/fluoropyrimidine doublet or triplet regimen
- Had proven clinical progression 6 months following (or during) last dose of adjuvant or neo-adjuvant therapy
- Human epidermal growth factor receptor 2 (HER2) negative status; or, those with HER2 positive status AND documented disease progression on a prior regimen containing trastuzumab
Who cannot join
- Chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to first dose of study intervention, or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better
- If major or minor surgery was performed at/near the area being considered for injection, participant must be recovered from toxicity and/or complications of intervention
- If participant has had injection or radiation therapy, participant must be recovered from toxicity and/or complications of intervention
- History of second malignancy, unless potentially curative treatment has been completed with no further evidence of disease for ≥5 years.
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with treated brain metastases may participate if lesions are radiologically stable.
- Active infection requiring therapy, except HIV criteria as stated above, and HBV and HCV criteria for HCC cohort as stated above
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- History of interstitial lung disease
- History of noninfectious pneumonitis requiring active steroid therapy or ongoing pneumonitis
- Active autoimmune disease that required systemic treatment in the past 2 years except vitiligo or resolved childhood asthma/atopy
- Known Hepatitis B or C infections or known to be positive for HBsAg/HBV deoxyribonucleic acid (DNA) or Hepatitis C Antibody or ribonucleic acid (RNA)
- History of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- Known hypersensitivity to gebasaxturev and/or pembrolizumab or any of their excipients
- Received prior therapy with anti-programmed cell death protein-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1) agents, Talimogene Laherparepvec (T-VEC), or any other oncolytic virus therapies
- Received a live or live-attenuated vaccine within 30 days prior to first dose of study intervention. Administration of killed vaccines is allowed.
- Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention
- Part 2, Cohort D:
- Has had esophageal or gastric variceal bleeding within the last 6 months
- Has had clinically diagnosed hepatic encephalopathy in the 6 months prior to initiation of study intervention
- Part 2, Cohort E:
- Squamous cell or undifferentiated gastric cancer
Trial locations and contacts
29 sites in 14 countries.
29 sites in 14 countries
Taiwan6 sites
Chang Gung Medical Foundation - Kaohsiung ( Site 0145)
Kaohsiung City, 833
China Medical University Hospital ( Site 0144)
Taichung, 40447
National Cheng Kung University Hospital ( Site 0142)
Tainan, 704
National Taiwan University Hospital ( Site 0141)
Taipei, 10002
Mackay Memorial Hospital ( Site 0143)
Taipei, 10449
Chang Gung Memorial Hospital - Linkou Branch ( Site 0146)
Taoyuan, 333
France3 sites
Hopital La Timone ( Site 0051)
Marseille, Bouches-du-Rhone, 13005
Centre Hospitalier Lyon-Sud ( Site 0055)
Pierre-Bénite, Auvergne-Rhône-Alpes, 69495
Gustave Roussy ( Site 0053)
Villejuif, Val-de-Marne, 94800
Israel3 sites
HaEmek Medical Center ( Site 0071)
Afula, 1834111
Hadassah Medical Center. Ein Kerem ( Site 0072)
Jerusalem, 9112001
Sourasky Medical Center ( Site 0073)
Tel Aviv, 6423906
United States2 sites
John Theurer Cancer Center ( Site 0004)
Hackensack, New Jersey, 07601
Providence Portland Medical Center ( Site 0001)
Portland, Oregon, 97213
Canada2 sites
Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0032)
Montreal, Quebec, H2X 3E4
Princess Margaret Cancer Centre ( Site 0031)
Toronto, Ontario, M5G 2M9
Germany2 sites
Universitaetsklinikum Heidelberg-Nationales Centrum für Tumorerkrankungen ( Site 0172)
Heidelberg, Baden-Wurttemberg, 69120
Universitaetsklinikum Tuebingen ( Site 0171)
Tübingen, Baden-Wurttemberg, 72076
Norway2 sites
Helse Bergen HF - Haukeland Universitetssykehus ( Site 0162)
Bergen, Hordaland, 5021
Oslo Universitetssykehus Radiumhospitalet ( Site 0161)
Oslo, 0379
Portugal2 sites
Centro Hospitalar Universitário Lisboa Norte, E.P.E. - Hospital de Santa Maria ( Site 0192)
Lisbon, Lisbon District, 1649-035
Instituto Português de Oncologia do Porto Francisco Gentil, EPE ( Site 0191)
Porto, 4200-072
Spain2 sites
Hospital Universitari Vall d Hebron ( Site 0121)
Barcelona, 08035
Clinica Universitaria de Navarra ( Site 0122)
Madrid, 28027
Italy1 site
Istituto Europeo di Oncologia IRCCS-Divisione di Sviluppo di Nuovi Farmaci per Terapie Innovative (
Milan, 20141
Japan1 site
National Cancer Center Hospital East ( Site 0166)
Kashiwa, Chiba, 277-8577
Poland1 site
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 0181
Warsaw, Masovian Voivodeship, 02-781
About this study
Official title: A Phase 1b/2 Clinical Study of Intratumoral Administration of V937 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic Solid Tumors
The purpose of this study is to evaluate the safety, tolerability, and efficacy in participants with advanced/metastatic or recurrent malignancies who receive gebasaxturev (V937) in combination with pembrolizumab (MK-3475). The primary objective for Part 1 is to evaluate the objective response rate, and the primary objective for Part 2 is to determine the safety and tolerability of gebasaxturev administered in combination with pembrolizumab. With Amendment 4, this study will be terminated once all participants who have completed or discontinued gebasaxturev treatment and are only receiving pembrolizumab may be enrolled in a pembrolizumab extension study, if available, to continue pembrolizumab monotherapy for up to 35 cycles from first pembrolizumab dose on V937-013.
- Conditions
- Neoplasm Metastasis
- Being tested
- Gebasaxturev, Pembrolizumab
- Keywords
- Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
- Medical subject headings
- Neoplasm Metastasis, Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GebasaxturevBiological
Also called Coxsackievirus A21 (CVA21), Formerly known as CAVATAK®, CAV21, V937
Participants receive gebasaxturev intratumorally for 1 28-day cycle followed by 7 21-day cycles.
PembrolizumabDrug
Also called MK-3475, KEYTRUDA®
Participants receive pembrolizumab intravenously for 1 28-day cycle followed by 34 21-day cycles.
| Study group | Role | What they receive |
|---|---|---|
| Part 1, Cohort A: Triple-Negative Breast Cancer | Experimental | This arm will enroll participants with triple-negative breast cancer (TNBC) solid tumors. Participants receive 3 X 10^8 50% tissue culture infectious dose (TCID50) of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days. Receives: Biological: Gebasaxturev; Drug: Pembrolizumab |
| Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma | Experimental | This arm will enroll participants with head and neck squamous cell carcinoma (HNSCC) solid tumors. Participants receive 3 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days. Receives: Biological: Gebasaxturev; Drug: Pembrolizumab |
| Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma | Experimental | This arm will enroll participants with cutaneous squamous cell carcinoma (cSCC) solid tumors. Participants receive 3 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days. Receives: Biological: Gebasaxturev; Drug: Pembrolizumab |
| Part 2 Dose Level 1, Solid Tumors + Liver Metastases | Experimental | This arm will enroll participants with solid tumors with liver metastases. Participants receive 3 X 10^7 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days. Receives: Biological: Gebasaxturev; Drug: Pembrolizumab |
| Part 2 Dose Level 2, Solid Tumors + Liver Metastases | Experimental | This arm will enroll participants with solid tumors with liver metastases. Participants receive 1 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days. Receives: Biological: Gebasaxturev; Drug: Pembrolizumab |
| Part 2 Dose Level 3, Solid Tumors + Liver Metastases | Experimental | This arm will enroll participants with solid tumors with liver metastases. Participants receive 3 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days. Receives: Biological: Gebasaxturev; Drug: Pembrolizumab |
| Part 2, Cohort D: Hepatocellular Carcinoma (HCC) | Experimental | This arm will enroll participants with hepatocellular carcinoma (HCC) solid tumors. Participants receive the gebasaxturev recommended phase 2 dose (RP2D) intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days. Receives: Biological: Gebasaxturev; Drug: Pembrolizumab |
| Part 2, Cohort E: Gastric Carcinoma | Experimental | This arm will enroll participants with gastric carcinoma solid tumors. Participants receive the gebasaxturev recommended phase 2 dose (RP2D) intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days. Receives: Biological: Gebasaxturev; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator
ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions and no new lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by investigator. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection does not render a lesion non-evaluable. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Measured: Up to approximately 30 months
Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
The following toxicities during DLT evaluation period were considered a DLT, if assessed by investigator to be possibly, probably, or definitely related to treatment: Grade (Gr) 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days, except Gr 3 thrombocytopenia (if associated with clinically significant bleeding) or any grade febrile neutropenia; nonhematologic adverse event (AE) ≥ Gr 3 (with exceptions); Gr 3 or 4 nonhematologic lab abnormality (if medical intervention is required, leads to hospitalization, or persists for >1 week); drug-related toxicity that causes a >2 week delay in Cycle 2 initiation; drug-related toxicity that causes treatment discontinuation or missed dosage of gebasaxturev; or Gr 5 toxicity. Per protocol, only the participants in Part 2 were analyzed in this outcome measure.
Measured: Cycle 1 (28-day cycle)
Part 2: Number of Participants Who Experienced One or More Adverse Events (AEs)
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Per protocol, only participants in Part 2 were analyzed in this outcome measure.
Measured: Up to approximately 29 months
Part 2: Number of Participants Who Discontinued Study Intervention Due to an AE
An AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Per protocol, only participants in Part 2 were analyzed in this outcome measure.
Measured: Up to approximately 10 months
Secondary outcomes (9)
Part 1: Number of Participants Who Experienced One or More AEs
An AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Measured: Up to approximately 30 months
Part 1: Number of Participants Who Discontinued Study Intervention Due to an AE
An AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Measured: Up to approximately 23 months
Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Investigator
PFS was defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by investigator. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection does not render a lesion non-evaluable. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Measured: Up to approximately 30 months
Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator
For participants who demonstrated a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by investigator, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death, whichever occurs first. For this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection did not render a lesion non-evaluable. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Measured: Up to approximately 30 months
PFS Per Response Evaluation Criteria in Solid Tumors 1.1 for Immune-Based Therapeutics (iRECIST) as Assessed by Investigator
PFS was defined as the time from first dose of study treatment to the first documented immune-based confirmed progressive disease (iCPD) or death due to any cause, whichever occurs first as assessed by investigator. Per iRECIST, iCPD was defined as worsening of any existing cause of progression, or the appearance of any other cause of progression, relative to the initial appearance of progressive disease by RECIST 1.1. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Measured: Up to approximately 30 months
DOR Per iRECIST as Assessed by Investigator
For participants who demonstrated confirmed CR (disappearance of all target lesions and non-target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 or immune-based Complete Response (iCR: Disappearance of all target lesions) or immune-based Partial Response (iPR: ≥30% decrease in the sum of diameters of target lesions) after a single PD per iRECIST, DOR was defined as the time from the first documented CR or PR, or iCR or an iPR, as assessed by investigator, until progressive disease or death, whichever occurs first. For this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection did not render a lesion non-evaluable. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Measured: Up to approximately 30 months
ORR Per iRECIST as Assessed by Investigator
ORR was defined as the percentage of participants who had confirmed responses assessed using RECIST 1.1 before PD or an immune-based Complete Response (iCR: Disappearance of all target lesions) or an immune-based Partial Response (iPR: ≥30% decrease in the sum of diameters of target lesions) after a single PD per iRECIST as assessed by investigator.
Measured: Up to approximately 30 months
Overall Survival (OS)
OS was defined as the time from first dose of study intervention to death due to any cause. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Measured: Up to approximately 30 months
Part 2: ORR Per RECIST 1.1 as Assessed by Investigator
ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions and no new lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by investigator. For this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection does not render a lesion non-evaluable. Per protocol, only participants in Part 2 were analyzed for this outcome measure.
Measured: Up to approximately 29 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2020
- Study start28 Oct 2020
- Primary completion25 Jul 2023
- Study completion25 Jul 2023
Why it stopped: Business Reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neoplasm MetastasisStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04521621
- Sponsor's protocol ID
- V937-013
- Other IDs
- V937-013, jRCT2033200191, 2020-001908-42
- Status last verified
- Sep 2024
- First submitted
- 17 Aug 2020
- Last updated
- 1 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
Deng JZ, Rustandi RR, Barbacci D, Swartz AR, Gulasarian A, Loughney JW. Reverse-Phase Ultra-Performance Chromatography Method for Oncolytic Coxsackievirus Viral Protein Separation and Empty to Full Capsid Quantification. Hum Gene Ther. 2022 Jul;33(13-14):765-775. doi: 10.1089/hum.2022.013. Epub 2022 Jun 1.
PubMed 35387488
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2 Clinical Study of Intratumoral Administration of V937 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT04521621
- Acronym / sponsor ID
- V937-013
- Conditions
- Neoplasm Metastasis
- Keywords
- Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business Reasons
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 28 Oct 2020 (actual)
- Primary completion
- 25 Jul 2023 (actual)
- Study completion
- 25 Jul 2023 (actual)
- First posted
- 20 Aug 2020 (actual)
- Results
- Posted 7 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety, tolerability, and efficacy in participants with advanced/metastatic or recurrent malignancies who receive gebasaxturev (V937) in combination with pembrolizumab (MK-3475). The primary objective for Part 1 is to evaluate the objective response rate, and the primary objective for Part 2 is to determine the safety and tolerability of gebasaxturev administered in combination with pembrolizumab. With Amendment 4, this study will be terminated once all participants who have completed or discontinued gebasaxturev treatment and are only receiving pembrolizumab may be enrolled in a pembrolizumab extension study, if available, to continue pembrolizumab monotherapy for up to 35 cycles from first pembrolizumab dose on V937-013.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Part 1, Cohort A: Triple-Negative Breast Cancer | Experimental | Biological: Gebasaxturev, Drug: PembrolizumabThis arm will enroll participants with triple-negative breast cancer (TNBC) solid tumors. Participants receive 3 X 10^8 50% tissue culture infectious dose (TCID50) of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days. |
| Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma | Experimental | Biological: Gebasaxturev, Drug: PembrolizumabThis arm will enroll participants with head and neck squamous cell carcinoma (HNSCC) solid tumors. Participants receive 3 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days. |
| Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma | Experimental | Biological: Gebasaxturev, Drug: PembrolizumabThis arm will enroll participants with cutaneous squamous cell carcinoma (cSCC) solid tumors. Participants receive 3 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days. |
| Part 2 Dose Level 1, Solid Tumors + Liver Metastases | Experimental | Biological: Gebasaxturev, Drug: PembrolizumabThis arm will enroll participants with solid tumors with liver metastases. Participants receive 3 X 10^7 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days. |
| Part 2 Dose Level 2, Solid Tumors + Liver Metastases | Experimental | Biological: Gebasaxturev, Drug: PembrolizumabThis arm will enroll participants with solid tumors with liver metastases. Participants receive 1 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days. |
| Part 2 Dose Level 3, Solid Tumors + Liver Metastases | Experimental | Biological: Gebasaxturev, Drug: PembrolizumabThis arm will enroll participants with solid tumors with liver metastases. Participants receive 3 X 10^8 TCID50 of gebasaxturev intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days. |
| Part 2, Cohort D: Hepatocellular Carcinoma (HCC) | Experimental | Biological: Gebasaxturev, Drug: PembrolizumabThis arm will enroll participants with hepatocellular carcinoma (HCC) solid tumors. Participants receive the gebasaxturev recommended phase 2 dose (RP2D) intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days. |
| Part 2, Cohort E: Gastric Carcinoma | Experimental | Biological: Gebasaxturev, Drug: PembrolizumabThis arm will enroll participants with gastric carcinoma solid tumors. Participants receive the gebasaxturev recommended phase 2 dose (RP2D) intratumorally for 8 cycles, and pembrolizumab intravenously for a maximum of 35 cycles. Cycle 1 is 28 days, and cycles 2-35 are 21 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (39 listed)
- Locally-advanced disease that is not amenable to surgery or radiation, or Stage IV advanced/metastatic solid tumor malignancies
- Histologically- or cytologically-confirmed diagnosis of an advanced/metastatic solid tumor.
- Measurable disease by RECIST 1.1 criteria as assessed by investigator. Target lesions in a previously irradiated area will be considered measurable if progression has been demonstrated in such lesions
- Submitted a baseline tumor sample for analysis. Participants enrolling in Part 2 Cohorts D-F may enroll without submitting a tumor sample if all other enrollment criteria are met.
- Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale obtained within 72 hours prior to the first dose of study intervention
Key exclusion criteria (20 listed)
- Chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to first dose of study intervention, or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better
- If major or minor surgery was performed at/near the area being considered for injection, participant must be recovered from toxicity and/or complications of intervention
- If participant has had injection or radiation therapy, participant must be recovered from toxicity and/or complications of intervention
- History of second malignancy, unless potentially curative treatment has been completed with no further evidence of disease for ≥5 years.
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with treated brain metastases may participate if lesions are radiologically stable.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GebasaxturevAlso: Coxsackievirus A21 (CVA21), Formerly known as CAVATAK®, CAV21, V937Participants receive gebasaxturev intratumorally for 1 28-day cycle followed by 7 21-day cycles. | Biological | Part 1, Cohort A: Triple-Negative Breast Cancer, Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma, Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma, Part 2 Dose Level 1, Solid Tumors + Liver Metastases, Part 2 Dose Level 2, Solid Tumors + Liver Metastases, Part 2 Dose Level 3, Solid Tumors + Liver Metastases, Part 2, Cohort D: Hepatocellular Carcinoma (HCC), Part 2, Cohort E: Gastric Carcinoma |
| PembrolizumabAlso: MK-3475, KEYTRUDA®Participants receive pembrolizumab intravenously for 1 28-day cycle followed by 34 21-day cycles. | Drug | Part 1, Cohort A: Triple-Negative Breast Cancer, Part 1, Cohort B: Head and Neck Squamous Cell Carcinoma, Part 1, Cohort C: Cutaneous Squamous Cell Carcinoma, Part 2 Dose Level 1, Solid Tumors + Liver Metastases, Part 2 Dose Level 2, Solid Tumors + Liver Metastases, Part 2 Dose Level 3, Solid Tumors + Liver Metastases, Part 2, Cohort D: Hepatocellular Carcinoma (HCC), Part 2, Cohort E: Gastric Carcinoma |
Primary outcome
Part 1: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator
Time frame: Up to approximately 30 months
ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions and no new lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by investigator. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and to specify that intratumoral injection does not render a lesion non-evaluable. Per protocol, only participants in Part 1 were analyzed in this outcome measure.
Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
Time frame: Cycle 1 (28-day cycle)
The following toxicities during DLT evaluation period were considered a DLT, if assessed by investigator to be possibly, probably, or definitely related to treatment: Grade (Gr) 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days, except Gr 3 thrombocytopenia (if associated with clinically significant bleeding) or any grade febrile neutropenia; nonhematologic adverse event (AE) ≥ Gr 3 (with exceptions); Gr 3 or 4 nonhematologic lab abnormality (if medical intervention is required, leads to hospitalization, or persists for >1 week); drug-related toxicity that causes a >2 week delay in Cycle 2 initiation; drug-related toxicity that causes treatment discontinuation or missed dosage of gebasaxturev; or Gr 5 toxicity. Per protocol, only the participants in Part 2 were analyzed in this outcome measure.
Part 2: Number of Participants Who Experienced One or More Adverse Events (AEs)
Time frame: Up to approximately 29 months
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Per protocol, only participants in Part 2 were analyzed in this outcome measure.
Part 2: Number of Participants Who Discontinued Study Intervention Due to an AE
Time frame: Up to approximately 10 months
An AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Per protocol, only participants in Part 2 were analyzed in this outcome measure.
9 secondary outcomes
Part 1: Number of Participants Who Experienced One or More AEs
Time frame: Up to approximately 30 months
Part 1: Number of Participants Who Discontinued Study Intervention Due to an AE
Time frame: Up to approximately 23 months
Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Investigator
Time frame: Up to approximately 30 months
Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator
Time frame: Up to approximately 30 months
PFS Per Response Evaluation Criteria in Solid Tumors 1.1 for Immune-Based Therapeutics (iRECIST) as Assessed by Investigator
Time frame: Up to approximately 30 months
DOR Per iRECIST as Assessed by Investigator
Time frame: Up to approximately 30 months
ORR Per iRECIST as Assessed by Investigator
Time frame: Up to approximately 30 months
Overall Survival (OS)
Time frame: Up to approximately 30 months
Part 2: ORR Per RECIST 1.1 as Assessed by Investigator
Time frame: Up to approximately 29 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35387488Deng JZ, Rustandi RR, Barbacci D, Swartz AR, Gulasarian A, Loughney JW. Reverse-Phase Ultra-Performance Chromatography Method for Oncolytic Coxsackievirus Viral Protein Separation and Empty to Full Capsid Quantification. Hum Gene Ther. 2022 Jul;33(13-14):765-775. doi: 10.1089/hum.2022.013. Epub 2022 Jun 1.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
29 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Gebasaxturev and Pembrolizumab in people with Neoplasm Metastasis, run by Merck Sharp & Dohme LLC at 29 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 39 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in Taiwan, France, Israel, United States, Canada and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator (time frame: Up to approximately 30 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04521621, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2024.